Despite tremendous advancement in drug delivery, oral administration still remains the most convenient and preferred means of drug delivery due to its low cost, ease of administration and flexibility in formulation. However, conventional oral dosage forms (e.g. tablets, capsules) have several inherent limitations, including a limited control over drug release rates, lack of complete absorption of oral drugs due to variable and short gastrointestinal (GI) transit time, and high fluctuation in plasma drug levels due to multiple dosing frequency. Dosage forms with a prolonged gastric residence time (GRT) have been used to circumvent some of these problems. Gastro-retentive delivery systems have the potential to improve bioavailability and reduce drug wastage that show preferential solubility, stability or absorption in the stomach or the proximal part of the GI tract.
Several approaches to prolong the GRT have been proposed based on various mechanisms, such as buoyancy (floating drug dosage systems, FDDS), swelling/plug type, high density and mucoadhesion. The constant renewal and high turnover of mucus may reduce the effectiveness of mucoadhesive systems. Unlike the retention of swelling systems and high density systems in the pylorus and the pyloric antrum, respectively, floating systems do not adversely affect the motility of the stomach. As such, FDDS have been extensively studied to retain drug forms in the stomach. With this, various floating systems have thus been developed using different materials (e.g. lipids, hydroxypropyl methylcellulose (HPMC)-based hydrodynamically balanced systems and alginate beads containing gas-generating agents) for controlled delivery of drugs.
While conventional oral drug delivery devices involve monolithic systems whereby only one drug is loaded, basic economics and patient compliance would favor the realization of a single microcapsule that simultaneously entraps and releases multiple drugs in a controlled manner. A single carrier or “tablet” that encapsulates multiple drugs would allow for a reduction in the number of oral tablets to be taken, as well as in the dosing frequency (i.e. pill burden), which in turn may improve patient compliance. Drug-drug interactions can also be avoided if individual drug substances are further protected within particles. Such a technology could potentially be used to treat diseases that require multiple drug combinations, such as HIV, cancer, tuberculosis and lupus. Another therapeutic area whereby floating microcapsules could be explored is for the treatment of chronic gastritis and peptic ulcers.
Though floating single drug dosage forms have already been well-established, there is a dearth of studies demonstrating the encapsulation of particles loaded with different drugs, while maintaining good floatability. It is thus hypothesized that the encapsulation of drug-loaded particles within a larger hollow capsule would provide good buoyancy, along with controlled release of multiple drugs. The addition of oil into the capsule shell can provide this extra buoyancy. The manipulation of capsule/particle parameters, such as shell thickness, particle sizes, and polymer types, can be tuned to control drug release rates.